Primary open-angle glaucoma (POAG), a widespread, chronic disease, is classified by the World Health Organization as the third leading cause of blindness. As many as 67 million people suffer from glaucoma and 10% will lose vision in both eyes as a result. Even in developed countries with advanced medical care, fewer than half of those with glaucoma associated with clinically elevated intraocular pressure (IOP) are even aware of their condition.
The primary clinical feature of glaucoma is progressive damage to the optic nerve with the attendant loss of visual function. Although the mechanism for glaucomatous optic neuropathy is uncertain, elevation of IOP is considered a primary risk factor. As early as 1907, physicians recognized that control of IOP slowed the progression of the disease. Studies have shown that decreasing IOP to <18 mm Hg decreases the risk of developing glaucoma by 50%, and, in patients with glaucoma, halts the progression of visual field effects. Even patients with so called normal-tension glaucoma benefit from a reduction in IOP.
Therefore, IOP has become a surrogate, easily measured endpoint to define successful therapeutic interventions, both pharmacologic and surgical. These therapeutic interventions do not treat glaucoma directly. Instead they attack one of the most important risk factors, namely elevated IOP. Both drugs and surgical approaches effectively decrease IOP and minimize visual field loss. This implies that it is the decrease in IOP, and not the method of achieving it, that preserves visual function. However, drugs and surgically implanted passive valves have their own limitations.
To decrease IOP, most drugs either increase outflow of aqueous humor from the anterior chamber of the eye, e.g., prostaglandin F2α, or decrease its production, e.g., beta-adrenergic blockers and carbonic anhydrase inhibitors. Some drugs, such as alpha-adrenergic agonists, do both. Their effects vary depending upon the patient's compliance, the patient's physiology and biochemistry, pathological condition, presence of other drugs and other changes in the environment that can affect IOP.
Like hypertension, elevated IOP is not detected by the patient until end organ damage becomes apparent, in this case glaucomatous optic neuropathy. Since patients cannot detect an immediate benefit, their motivation to administer the drugs is lacking and patient compliance is often poor. In addition, drugs, even those applied topically, often cause adverse effects, are uncomfortable to apply in the eye, and present a significant, continuing expense.
Although the reduction of IOP by surgical methods also effectively reduces progression of visual defects, long-term control is rarely achieved. Existing approaches such as laser trabeculoplasty, trabeculectomy, and implantable valves require surgical implementation, have set points that cannot be controlled once implanted, and generally have variable control of IOP that can depend on rates of healing, aqueous humor production and other confounding factors. Although patient compliance is not a factor here, the surgical approach is often of limited effectiveness due to formation of fibrous scar tissue and may predispose patients to cataracts. In addition, when compared to medical therapy, surgical patients reported a slightly higher incidence of long term ocular burning, redness and dry eye.
A major limitation of existing approaches to treatment is that neither drugs nor surgical procedures are capable of automatically adjusting their actions based on the patient's IOP. This drawback is of particular concern because maintenance of IOP in POAG below 18 mm Hg is generally considered essential to decrease the onset of glaucomatous optic neuropathy (or, once established, prevent its progression). Normal-tension glaucoma patients typically require a lower set point of less than 11 mm Hg. In addition, the lack of adjustment further limits the utilization of any other drugs that may elevate or decrease IOP as one of their primary or side effects.
One method for treating glaucoma is to devise an artificial drainage shunt with a pressure-sensitive valve that allows aqueous humor to flow from the anterior chamber of the eye. However, existing valve-regulated devices are limited. Conventional valves are passive devices that often allow too little or occasionally too much drainage of aqueous humor. Another disadvantage is the inability to actively monitor IOP on a long-term basis. In addition, conventional devices, even when working optimally, cannot be adjusted once in place, which leaves the patient and the physician at the mercy of pre-existing valve parameters. Furthermore, these valves may fail and, therefore, must be removed due to poor control in terms of proper pressure regulation.
Therefore, there is a need for an automated system that will permit flexible and long-term monitoring and control of IOP in glaucoma patients. There is also a need for more efficient and consistent regulation of pressure for other biomedical or commercial applications. The present invention is directed to these and other ends.